Krivoy Norberto, Taer Masud, Neuman Manuela G
Department of Medicine B and Clinical Pharmacology Unit, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Curr Drug Saf. 2006 Aug;1(3):289-99. doi: 10.2174/157488606777934459.
Host dependent idiosyncratic drug reactions, otherwise known as unpredictable type B reactions, are of a major concern in clinical practice and drug development. Hypersensitivity syndrome reactions are idiosyncratic in nature and may be induced by a variety of agents including antiepileptic drugs (AEDs). The AEDs hypersensitivity syndrome is a rare but potentially life-threatening syndrome that occurs after exposure to phenytoin, carbamazepine or phenobarbital. Phenobarbital, phenytoin and carbamazepine, have shown cross-reactivity; while, no evidence of cross reactivity between other antiepileptic drugs such as valproic acid, gabapentin or lamotrigine has been observed. True hypersensitivity reaction is a systemic disease defined by the triad of fever, skin eruption and multi-organ involvement that occurs 1-8 weeks after exposure to a drug. Because most reactions occur within two months of treatment initiation, it is likely that the true incidence of the syndrome is underestimated. It was hypothesized that reactive metabolite/s (RM) rather than the parent drug, is/are responsible for initiating the sequence of toxic and immunological events that culminate clinically in a drug hypersensitivity syndrome reaction. Cells that possess surface antigens for which T cells have specific receptors then present this antigen. Exanthemas are related to delayed T-cell hypersensitivity so it has been hypothesized that memory T cells might subsequently increase in number in the most severely affected cutaneous sites. To manage hypersensitivity syndrome successfully, the symptoms must recognized early, the use of the offending drug must be terminated immediately, and alternative antiepileptic medication should be prescribed. Currently, the diagnosis of AEDs-induced hypersensitivity syndromes is based on clinical grounds and on in vitro testing. In the field of pharmacogenetics, we bare witness to how effectively the combination of effective screening methods and understanding of the role of genetic polymorphisms play in the metabolic pathways of AEDs facilitating new therapies that allow scientists and physicians to better diagnose and treat patients.
宿主依赖性特异质药物反应，又称不可预测的B型反应，是临床实践和药物研发中的主要关注点。超敏反应综合征本质上属于特异质反应，可能由包括抗癫痫药物（AEDs）在内的多种药物诱发。AEDs超敏反应综合征是一种罕见但可能危及生命的综合征，发生于接触苯妥英、卡马西平或苯巴比妥之后。苯巴比妥、苯妥英和卡马西平已显示存在交叉反应；而丙戊酸、加巴喷丁或拉莫三嗪等其他抗癫痫药物之间未观察到交叉反应的证据。真正的超敏反应是一种全身性疾病，其特征为发热、皮疹和多器官受累三联征，发生于接触药物后1至8周。由于大多数反应发生在开始治疗后的两个月内，该综合征的实际发病率很可能被低估。据推测，是反应性代谢物而非母体药物引发了一系列毒性和免疫事件，最终在临床上导致药物超敏反应综合征。具有T细胞特异性受体的表面抗原的细胞随后会呈递这种抗原。皮疹与迟发性T细胞超敏反应有关，因此据推测，记忆T细胞数量可能随后会在受影响最严重的皮肤部位增加。为成功处理超敏反应综合征，必须尽早识别症状，立即停用引发问题的药物，并应开具替代抗癫痫药物。目前，AEDs诱发的超敏反应综合征的诊断基于临床依据和体外检测。在药物遗传学领域，我们见证了有效的筛查方法与对基因多态性在AEDs代谢途径中的作用的理解相结合，如何有效地推动新疗法的出现，使科学家和医生能够更好地诊断和治疗患者。
